DESCRIPTION: (Applicant's Abstract) Methamphetamine (MA) dependence is expanding rapidly in the United States, recapitulating early phases of epidemic spread in the 1950's and 1960's. Beyond the morbidity and mortality directly associated with addictive disease, MA is of particular concern in light of the HIV epidemic because it is administered intravenously and because it increases libido. Catecholamine receptor proliferation in chronic MA use, and similarities between MA withdrawal and major depression, have long been known, yet minimal effort has been applied to determine whether pharmacotherapy may be of help in achieving abstinence from MA. Tyrosine is the dietary precursor to catecholamines, has yielded positive results in small trials of its antidepressant efficacy, completely blocks the norepinephrine depleting effects of MA in animals, and reduces MA self-administration in animals. This application proposes a 12 week, double-blind, placebo-controlled clinical trial to test the efficacy of tyrosine in reducing MA use in MA dependent subjects. One hundred subjects with DSM-IV diagnoses of MA dependence will be randomly assigned to receive either tyrosine, 2 grams, or placebo, three times daily. Subjects will receive medication for three months; follow-up evaluation will be conducted at month 4. Study medication will be added to intensive outpatient drug treatment. The study will be conducted at the Drug Detoxification, Rehabilitation and Aftercare Program of the Haight Ashbury Free Clinics, a community based, not-for-profit clinic in San Francisco, CA. Following completion of baseline measures, subjects will be assessed weekly to determine their compliance with study medications, to ascertain their use of MA and other drugs, to complete rating scales, to obtain a urine specimen, and to dispense their next week's supply of medication. Data collection instruments will include the Addiction Severity Index, the Symptom Checklist-90, the Beck Depression Inventory, the Risk for AIDS Behaviors, and the Treatment Services Review. Primary efficacy measures are: days of MA use, continuous abstinence, and treatment retention. Pre-planned analyses will use survival analyses and analysis of variance to compare tyrosine and placebo and gender by study drug interaction.